tbuckley/cabot-search huggingface dataset:
Real-world cost effectiveness of first-line pembrolizumab for advanced melanoma: A population-based study by the Canadian Real-world Evidence Value for Cancer Drugs (CanREValue) Collaboration.
Authors: Timothy Hanna, Suriya Aktar, Vanessa Arciero, Ning Liu, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2022)

17 Background: Randomized controlled trials (RCTs) demonstrate large survival benefits with anti-PD-1 checkpoint inhibitors compared to anti-CTLA4 therapy for advanced melanoma. However, it remains unclear if patients in routine practice derive a similar survival benefit or if real-world health utilization differs from trials. Outcomes are needed to inform life-cycle health technology reassessment (HTA) with real-world cost-effectiveness analysis. Methods: This study compared patients with advanced melanoma treated with publicly funded first-line ipilimumab (September 2012 - December 2014) or pembrolizumab (June 2016 - March 2018) in Ontario, Canada. These periods were chosen to reflect distinct eras of access to treatment. Linked administrative databases were used to identify cases, covariates, health-utilization and all-cause death. Inverse probability of treatment weighting (IPTW) with stabilizing weights was used to adjust for covariates (including: age, sex, melanoma site, rurality, income, comorbidity, stage at diagnosis, cancer history, prior brain metastasis treatment). Using a three-year time horizon, individual patient-level censoring-adjusted costs in 2019 Canadian dollars with a 1.5% annual discount rate were determined from the public payer’s perspective. The outcome was quality-adjusted life-years (QALY) measured at the individual patient level. Health utilities were based on accepted Canadian values from the initial HTA. The incremental cost-effectiveness ratio (ICER) was determined with bootstrap confidence intervals (CI). Results: Ninety patients treated with first-line ipilimumab, and 300 with pembrolizumab were identified. Those receiving pembrolizumab were older (median 70 vs.63 years), more likely to have multiple comorbidities (12% vs. 8%), and no prior brain radiation (83% vs. 74%). Covariates were balanced after weighting. Pembrolizumab was associated with improved OS (43.1% vs. 22.1% with ipilimumab at 3 years, IPTW adjusted hazard ratio: 0.52, 95% CI: 0.39-0.70; p &lt; 0.001). Mean costs for pembrolizumab and ipilimumab were $212,706 (95% CI 196,122 - 229,290) and $158,352 ($143,218 - 173,484), and mean survival 1.20 QALY (95%CI 1.11 – 1.29) and 0.66 QALY (0.52 – 0.80) respectively. The ICER was $101,183/QALY (65,375 – 139,298). The probability of cost-effectiveness was 0%, 48% and 99% at willingness-to-pay thresholds of $50k, $100k and $150k respectively. Conclusions: In real-world patients, first-line pembrolizumab for advanced melanoma was associated with improved OS compared to ipilimumab. The real-world cost-effectiveness estimate of $101,183/QALY is similar to the model-based cost-effectiveness estimates ($114,389/QALY to $151,369/QALY) used in the initial health technology assessment recommendation prior to reimbursement.
Association of clinic type with receipt of neoadjuvant therapy among patients with localized pancreatic cancer: Value of multidisciplinary clinic.
Authors: Priya Pathak, Amy Hacker-Prietz, Joseph M. Herman, Lei Zheng, Jin He, Amol Narang
Journal: Journal of Clinical Oncology (2022)

63 Background: Patients with localized pancreatic adenocarcinoma (PDAC) generally benefit from multi-modality therapy, which may be best coordinated through a pancreas multi-disciplinary clinic (PMDC). Whether treatment practice patterns vary based on whether a patient was seen through PMDC versus individual specialty-specific clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients who came to Johns Hopkins Hospital through either PMDC or one of the individual surgical, medical, or radiation oncology clinics for localized PDAC between 2018-2020 and eventually underwent resection. During this time, it was standard practice for borderline resectable (BRPC) patients to undergo at least 4 months of neoadjuvant chemotherapy, with or without radiation, before transitioning to exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation, followed by potential exploration. The primary outcome was completion of neoadjuvant therapy as per the above stage-specific institutional standards. Multivariable analyses were performed to find association between PMDC visit and completion of neoadjuvant therapy, controlling for age, sex, race, stage, baseline performance status and type of chemotherapy. Results: A total of 240 patients met inclusion criteria. Of these, 157 (65.4%) had PMDC visits. Distribution of stage across the cohort included 81 (34.3%), 91 (38.5%), and 64 (27.1%) patients with resectable PDAC, BRPC and LAPC, respectively. Patients in the PMDC group received radiation therapy more commonly (59.7% vs 34.9%, p = 0.004), as compared to patients seen through individual specialty-specific clinics. Mean duration of chemotherapy was higher for patients seen through PMDC (4.4 (SD: 1.7) vs 3.9 (SD: 2.0) months) compared with individual clinics. Completion of neoadjuvant therapy per institutional stage-specific standards was seen in 46% (n = 24) of the patients visiting individual specialty-specific clinics compared to 71% (n = 85) of patients who were seen through PMDC (p = 0.002). The adjusted odds ratio of completion of neoadjuvant therapy per institutional standards for patients seen through PMDC visit was 3.35 times the odds for patients seen through individual clinics (95% CIs 1.46-7.07; p = 0.004). Of note, a higher proportion of patients who were seen through PMDC enrolled in a clinical trial (n = 26, 16.6%) compared with patients seen through individual clinics (n = 6; 7.2%) (p = 0.043). Conclusions: Provision of care through a multi-disciplinary clinic was associated with significantly higher odds of completing neoadjuvant therapy per institutional standards as compared to care through individual specialty-specific clinics. In addition, care through a PMDC may also be associated with increased trial enrollment.
Comparative efficacy of different treatment modalities in the management of pediatric non-alcoholic fatty liver disease: A systematic review and network meta-analysis
Authors: Xenophon Theodoridis, Georgios Kalopitas, Andreas Vadarlis, Dimitra Rafailia Bakaloudi, Νikolaos Gkiourtzis, Georgios Dionysopoulos, Evangelia Karanika, Eirini Tsekitsidi, Michail Chourdakis
Journal: Pharmacology & Therapeutics (2022)
Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
Authors: Sébastien Leblanc, Marie A. Brunet, Jean-François Jacques, Amina M. Lekehal, Andréa Duclos, Alexia Tremblay, Alexis Bruggeman-Gascon, Sondos Samandi, Mylène Brunelle, Alan A. Cohen, Michelle S. Scott, Xavier Roucou
Journal: Genomics Proteomics & Bioinformatics (2022)
A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence
Authors: Tao He, Mingxing Hu, Shunyao Zhu, Meiling Shen, Xiaorong Kou, Xiuqi Liang, Lu Li, Xinchao Li, Miaomiao Zhang, Qinjie Wu, Changyang Gong
Journal: Acta Pharmaceutica Sinica B (2022)

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.
Sentinel lymph node biopsy in patients with T1a cutaneous malignant melanoma: A multicenter cohort study
Authors: Adrienne B. Shannon, Cimarron E. Sharon, Richard J. Straker, Michael J. Carr, Andrew J. Sinnamon, Kita Bogatch, Alexandra Thaler, Nicholas Kelly, John T. Vetto, Graham Fowler, Danielle DePalo, Vernon K. Sondak, John T. Miura, Mark B. Faries, Edmund K. Bartlett, Jonathan S. Zager, Giorgos C. Karakousis
Journal: Journal of the American Academy of Dermatology (2022)
Ironing out exercise on immuno-oncological outcomes
Authors: Janjira Soh, Zi Xiang Lim, Elaine Hsuen Lim, Brian K Kennedy, Jorming Goh
Journal: Journal for ImmunoTherapy of Cancer (2022)

Despite accumulating evidence that supports the beneficial effects of physical exercise in inhibiting cancer progression, whether exercise modulates its effects through systemic and cellular changes in iron metabolism and immune-tumor crosstalk is unknown. Cancer cells have greater metabolic requirements than normal cells, with their survival and proliferation depending largely on iron bioavailability. Although iron is an essential mineral for mitogenesis, it also participates in a form of iron-dependent programmed cell death termed ferroptosis. In this short hypothesis paper, we speculate that modulating iron bioavailability, transport and metabolism with regular exercise can have significant implications for tumor and stromal cells in the tumor microenvironment, by affecting multiple tumor-autonomous and stromal cell responses.
Identification of novel HLA-A*11:01-restricted HPV16 E6/E7 epitopes and T-cell receptors for HPV-related cancer immunotherapy
Authors: Chengjie Xiong, Lihong Huang, Hedan Kou, Chenwei Wang, Xiaomin Zeng, Hanli Sun, Shangyuan Liu, Bin Wu, Jingyao Li, Xiaoling Wang, Zibing Wang, Lin Chen
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background E6 and E7 oncoproteins are considered ideal antigens of T cell therapy for human papillomavirus (HPV)-related cancers. However, little is known about the epitopes of E6 and E7 presented by HLA-A*11:01, one of the most prevalent HLA types globally, especially in Asia. Methods We combined in silico and experimental approaches to identify endogenously processed HLA-A*11:01-restricted epitopes of HPV16 E6 and E7. The identified epitopes were then used to screen available T cell receptors (TCRs) from healthy donors through in vitro stimulation of peripheral blood mononuclear cells (PBMCs). Results E6 93-101 (TTLEQQYNK, TTL) and E7 89-97 (IVCPICSQK, IVC), two novel HLA-A*11:01-restricted T cell epitopes of HPV16, were identified to be endogenously presented on tumor cells. TTL- and IVC-specific TCRs were isolated from 11 healthy donors through in vitro stimulation of PBMC. The key TTL and IVC residues involved in TCR-pMHC interactions were mapped, and the consensus sequence was “xxLEQxYNK” and “xVxPIxxxK.” The TTL- and IVC-specific TCRs with high functional avidity were used to generate TCR-engineered T cells, specifically recognizing and killing corresponding tumor cell lines in vitro and in vivo. In addition, TTL and IVC-specific TCR-T cells also recognized and killed HPV16 + patient-derived organoids. Conclusions The HLA-A*11:01-restricted HPV16 E6/E7 epitopes and TCRs identified in this study may provide a new strategy for HPV-related cancer immunotherapy in HLA-A*11:01 + patients.
Artificial intelligence and radiomics: fundamentals, applications, and challenges in immunotherapy
Authors: Laurent Dercle, Jeremy McGale, Shawn Sun, Aurelien Marabelle, Randy Yeh, Eric Deutsch, Fatima-Zohra Mokrane, Michael Farwell, Samy Ammari, Heiko Schoder, Binsheng Zhao, Lawrence H Schwartz
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immunotherapy offers the potential for durable clinical benefit but calls into question the association between tumor size and outcome that currently forms the basis for imaging-guided treatment. Artificial intelligence (AI) and radiomics allow for discovery of novel patterns in medical images that can increase radiology’s role in management of patients with cancer, although methodological issues in the literature limit its clinical application. Using keywords related to immunotherapy and radiomics, we performed a literature review of MEDLINE, CENTRAL, and Embase from database inception through February 2022. We removed all duplicates, non-English language reports, abstracts, reviews, editorials, perspectives, case reports, book chapters, and non-relevant studies. From the remaining articles, the following information was extracted: publication information, sample size, primary tumor site, imaging modality, primary and secondary study objectives, data collection strategy (retrospective vs prospective, single center vs multicenter), radiomic signature validation strategy, signature performance, and metrics for calculation of a Radiomics Quality Score (RQS). We identified 351 studies, of which 87 were unique reports relevant to our research question. The median (IQR) of cohort sizes was 101 (57–180). Primary stated goals for radiomics model development were prognostication (n=29, 33.3%), treatment response prediction (n=24, 27.6%), and characterization of tumor phenotype (n=14, 16.1%) or immune environment (n=13, 14.9%). Most studies were retrospective (n=75, 86.2%) and recruited patients from a single center (n=57, 65.5%). For studies with available information on model testing, most (n=54, 65.9%) used a validation set or better. Performance metrics were generally highest for radiomics signatures predicting treatment response or tumor phenotype, as opposed to immune environment and overall prognosis. Out of a possible maximum of 36 points, the median (IQR) of RQS was 12 (10–16). While a rapidly increasing number of promising results offer proof of concept that AI and radiomics could drive precision medicine approaches for a wide range of indications, standardizing the data collection as well as optimizing the methodological quality and rigor are necessary before these results can be translated into clinical practice.
Targeting inflammatory macrophages rebuilds therapeutic efficacy of DOT1L inhibition in hepatocellular carcinoma
Authors: Yi-Bin Yang, Cai-Yuan Wu, Xu-Yan Wang, Jia Deng, Wen-Jie Cao, Yun-Zhi Tang, Chao-Chao Wan, Zhi-Tian Chen, Wan-Yu Zhan, Hong Shan, Dong-Ming Kuang, Yuan Wei
Journal: Molecular Therapy (2022)

Epigenetic reprogramming is a promising therapeutic strategy for aggressive cancers, but its limitations in vivo remain unclear. Here, we showed, in detailed studies of data regarding 410 patients with human hepatocellular carcinoma (HCC), that increased histone methyltransferase DOT1L triggered epithelial-mesenchymal transition-mediated metastasis and served as a therapeutic target for human HCC. Unexpectedly, although targeting DOT1L in vitro abrogated the invasive potential of hepatoma cells, abrogation of DOT1L signals hardly affected the metastasis of hepatoma in vivo. Macrophages, which constitute the major cellular component of the stroma, abrogated the anti-metastatic effect of DOT1L targeting. Mechanistically, NF-κB signal elicited by macrophage inflammatory response operated via a non-epigenetic machinery to eliminate the therapeutic efficacy of DOT1L targeting. Importantly, therapeutic strategy combining DOT1L-targeted therapy with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited cancer regression. Moreover, we found that the densities of macrophages in HCC determined malignant cell DOT1L-associated clinical outcome of the patients. Our results provide insight into the crosstalk between epigenetic reprogramming and cancer microenvironments and suggest that strategies to influence the functional activities of inflammatory cells may benefit epigenetic reprogramming therapy.
Podocyte expression of human phospholipase A2 receptor 1 causes immune-mediated membranous nephropathy in mice
Authors: Nicola M. Tomas, Silke Dehde, Catherine Meyer-Schwesinger, Ming Huang, Irm Hermans-Borgmeyer, Johanna Maybaum, Renke Lucas, Jennie L. von der Heide, Oliver Kretz, Sarah M.S. Köllner, Larissa Seifert, Tobias B. Huber, Gunther Zahner
Journal: Kidney International (2022)
Hypercalcemia in Malignant Lymphoma
Authors: Jacob Lokich
Journal: JAMA (1979)

HYPERCALCEMIA with or without secondary clinical manifestations develops in up to 10% of patients with malignant disease—most commonly in patients with lung and breast cancer, but also in association with prostate cancer, multiple myeloma, and renal cell tumors. The development of hypercalcemia in malignant lymphomas of the Hodgkin's and non-Hodgkin's type is rare.<sup>1,2</sup>The mechanism of the hypercalcemia is not established, but may be associated with the ectopic secretion of a parathormone-like substance or other substances, such as prostaglandin or osteoclast-activating factor, that induce bone resorption. This report of a patient with malignant lymphoma and associated hypercalcemia 17 years following complete surgical parathyroidectomy indicates that the hypercalcemia is not mediated through the parathyroid axis involving endogenous parathormone. <h3>Report of a Case</h3> A 70-year-old woman was admitted to the New England Deaconess Hospital, Boston, for evaluation and treatment of hypercalcemia. In 1961, she had undergone total thyroidectomy for what was
Improving Health Care for the Poor
Authors: Sumana Reddy
Journal: JAMA (1994)

<h3>To the Editor.</h3> —I read the article by Dr Ginzberg<sup>1</sup>with great interest and largely with agreement. Trained in rural health care and working with migrant farm workers in a California community clinic as I do, the degree of abandonment of indigent care by the medical profession at large has seemed remarkable. However, I take strong exception to his passing and demeaning reference to international medical graduates (IMGs). As a US-born and University of Toronto— and University of California—San Francisco—trained physician myself, I am stunned by his lack of awareness. Rather than being of "indifferent professional competence" and "with language problems that impede effective communication," IMGs constitute a highly skilled group. Thanks to an effective maintenance of local monopolies, the medical profession has long denied IMGs their fair due. Only the best of the foreign graduates make it through the testing and interview processes. They provide care in regions
Dynamic photoelectrical regulation of ECM protein and cellular behaviors
Authors: Xiaozhao Wang, Cai Yao, Xudong Yao, Junxin Lin, Rui Li, Kun Huang, Weiming Lin, Xiaojun Long, Chao Dai, Jiajun Dong, Xuegong Yu, Wenwen Huang, Wenjian Weng, Qi Wang, Hongwei Ouyang, Kui Cheng
Journal: Bioactive Materials (2022)

Dynamic regulation of cell-extracellular matrix (ECM)-material interactions is crucial for various biomedical applications. In this study, a light-activated molecular switch for the modulation of cell attachment/detachment behaviors was established on monolayer graphene (Gr)/n-type Silicon substrates (Gr/Si). Initiated by light illumination at the Gr/Si interface, pre-adsorbed proteins (bovine serum albumin, ECM proteins collagen-1, and fibronectin) underwent protonation to achieve negative charge transfer to Gr films (n-doping) through π-π interactions. This n-doping process stimulated the conformational switches of ECM proteins. The structural alterations in these ECM interactors significantly reduced the specificity of the cell surface receptor-ligand interaction (e.g., integrin recognition), leading to dynamic regulation of cell adhesion and eventual cell detachment. RNA-sequencing results revealed that the detached bone marrow mesenchymal stromal cell sheets from the Gr/Si system manifested regulated immunoregulatory properties and enhanced osteogenic differentiation, implying their potential application in bone tissue regeneration. This work not only provides a fast and feasible method for controllable cells/cell sheets harvesting but also gives new insights into the understanding of cell-ECM-material communications.
Respiratory Distress Syndrome
Authors: A MALDONADO, M DOMPER, M J GARCIA, J ARBIZU, S MARTIN, J RICHTER
Journal: Clinical Nuclear Medicine (1993)

An esophagobronchial fistula developed in a patient who had well-differentiated squamous carcinoma of the lung that was treated with chemotherapy. Because the esophagobronchial fistula could not be surgically repaired, it was isolated with a mechanical stitch above and below it. Forty-eight hours after initiation of enteral nutrition, a perfusion lung scan was performed because of clinical suspicion of pulmonary embolism. Because the scan showed reduced pulmonary radioactivity and accumulation of activity in the kidneys and spine, an arteriovenous shunt was suspected. However, subsequent digital substraction angiography ruled out this possibility and a recurrence of the esophagobronchial fistula was confirmed with an esophagogram. The unusual extrapulmonary activity could be related to a reversible capillary shunt in the pulmonary vasculature, secondary to acute respiratory distress syndrome.
Cyclophosphamide vs Melphalan in Myeloma
Authors: John M. Bennett
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Drs. Rivers and Patno (<b>207</b>:1328, 1969) have clearly demonstrated that cyclophosphamide and melphalan are equally effective chemotherapeutic agents in plasma cell myeloma. I am impressed, however, by the striking difference between the median survival of the placebo group from an earlier study (15 weeks) and that of the "no response" group of the present series (48 weeks). Is it possible to attribute this threefold increase in longevity to the use of drugs despite any objective or subjective response data? It has become increasingly apparent that survival in many hematopoietic malignancies including Hodgkin's disease and plasma cell myeloma is a function not only of chemotherapy or radiotherapy but also relates to the number of objective and subjective prognostic factors present during initial evaluation.<sup>1</sup>An intriguing possibility is that with increased diagnostic acumen, including immunoelectrophoresis, myeloma patients are being uncovered at an earlier stage of their disease. In